- Copper-Mediated Radiosynthesis of [18F]Rucaparib
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The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the 18F-isotopologue of rucaparib by applying a copper-mediated nucleophilic 18F-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-18F-labeling and affords [18F]rucaparib with an activity yield of 11% ± 3% (n = 3) and a molar activity (Am) up to 30 GBq/μmol. Preliminary in vitro studies are presented.
- Chen, Zijun,Destro, Gianluca,Guibbal, Florian,Chan, Chung Ying,Cornelissen, Bart,Gouverneur, Véronique
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supporting information
p. 7290 - 7294
(2021/09/14)
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- METHODS AND INTERMEDIATES FOR PREPARING RUCAPARIB
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The present invention relates to a process for preparing rucaparib or pharmaceutically acceptable salts thereof. It also provides novel intermediates that may be converted into rucaparib or pharmaceutically acceptable salts thereof.
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Page/Page column 29
(2019/07/17)
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- SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS
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Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
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Page/Page column 55; 56
(2018/06/06)
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- Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides
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As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide car-bonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor elec-trophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nu-cleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.
- Nakajima, Minami,Oda, Yukiko,Wada, Takamasa,Minamikawa, Ryo,Shirokane, Kenji,Sato, Takaaki,Chida, Noritaka
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p. 17565 - 17571
(2015/02/19)
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- Smooth isoindolinone formation from isopropyl carbamates via bischler-napieralski-type cyclization
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Isopropyl carbamates derived from benzylamines provide isoindolinones by treatment with phosphorus pentoxide at room temperature. Utility of this Bischler-Napieralski-type cyclization and a new mechanism involving a carbamoyl cation for rationalization of this smooth conversion are discussed.
- Adachi, Satoshi,Onozuka, Masao,Yoshida, Yuko,Ide, Mitsuaki,Saikawa, Yoko,Nakata, Masaya
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supporting information
p. 358 - 361
(2014/04/03)
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- Highly enantioselective synthesis of tetrahydroquinolines via cobalt(II)-catalyzed tandem 1,5-hydride transfer/cyclization
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A chiral catalyst prepared from N,N′-dioxide and Co(BF 4)2·6H2O was applied in the asymmetric hydride transfer initiated cyclization reaction, giving optically active tetrahydroquinolines in good yields with high enantioselectivities under mild reaction conditions. Meanwhile, in light of the absolute configuration of the product, a possible working model was proposed to explain the origin of the activation and asymmetric induction.
- Cao, Weidi,Liu, Xiaohua,Wang, Wentao,Lin, Lili,Feng, Xiaoming
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p. 600 - 603
(2011/04/15)
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- NOVEL BIS-AMIDES AS ANTI-MALARIAL AGENTS
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The invention relates to novel bis-amide derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including pharmaceutical compositions containing one or more of those compounds and their use as medicaments for the treatment or prevention of protozoal infections, such as especially malaria.
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Page/Page column 54
(2011/10/04)
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- LINCOMYCIN DERIVATIVES AND ANTIBACTERIAL AGENTS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
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An objective of the present invention is to provide compounds of formula (1) or their pharmacologically acceptable salts or solvates wherein A represents aryl; R1 represents N-optionally substituted C1-6 alkyl-N-optionally substituted C1-6 alkylamino-C1-6 alkyl; R2 represents a hydrogen atom or optionally substituted C1-6 alkyl; R3 represents optionally substituted C1-6alkyl or C3-6 cycloalkyl-C1-4 alkyl; m is 1 to 3; n is 0; and p is 0 to 2. The compounds are novel lincomycin derivatives that have a potent activity against resistant Streptococcus pneumoniae, which have recently posed problems, in the treatment of infectious diseases. Further, the compounds are usable as antimicrobial agents and are useful for preventing or treating bacterial infectious diseases.
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Page/Page column 41
(2010/03/02)
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- NOVEL BIS-AMIDES AS ANTIMALARIAL AGENTS
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The invention relates to novel bis-amide derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including pharmaceutical compositions containing one or more of those compounds and their use as medicaments for the treatment or prevention of protozoal infections, such as especially malaria.
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Page/Page column 77-78
(2010/07/10)
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- Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigations
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3H-1,3,4-Oxadiazol-2-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Oxadiazolone derivatives showed an interesting antimycobacterial activity against the reference strain of Mycobacterium tuberculosis H37Rv. Molecular modeling investigations were performed and showed that the active compounds possess all necessary features to target the protein active site of the mycobacterial cytochrome P450-dependent sterol 14α-demethylase in the sterol biosynthesis pathway as the calculated free energy of binding were in agreement with the corresponding MIC values.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Fermeglia, Maurizio,Posocco, Paola,Pricl, Sabrina,Banfi, Elena,Scialino, Giuditta,Vio, Luciano
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experimental part
p. 4693 - 4707
(2009/10/24)
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- (HETERO)ARYL COMPOUNDS WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
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The present invention relates to (hetero)aryl compounds of general formula (I) wherein the groups and radicals A, B, Q, W, X, Y, Z, R1, R2, R4a, R4b, R5a, R5b, have the meanings given in cl
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Page/Page column 76
(2010/11/27)
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- Synthesis of a new water-soluble C2-symmetric chiral diamine: Preliminary investigation of its catalytic properties for asymmetric hydrogenation under biphasic conditions
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A water-soluble version of N,N′-dimethyl-1,2-diphenylethane-1,2-diamine was prepared by introduction of phosphonic acid moieties on the para position of the aromatic rings. Preliminary investigation of the catalytic properties of the iridium complex of this ligand under biphasic conditions showed that this system compared well with the homogeneous counterpart for the asymmetric hydrogenation of ketones but with noticeably higher reaction rates for the biphasic system.
- Maillet, Celine,Praveen, Thoniyot,Janvier, Pascal,Minguet, Sebastien,Evain, Michel,Saluzzo, Christine,Tommasino, M. Lorraine,Bujoli, Bruno
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p. 8191 - 8196
(2007/10/03)
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- N,N-disubstituted arylcycloalkylamines, the salts thereof, pharmaceutical compositions containing these compounds and the use thereof and processes for preparing them
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The invention relates to N,N-disubstituted arylcycloalkylamines of general formula STR1 wherein n, m, A, X and R1 to R7 are defined as in claim 1, the isomers, isomer mixtures and salts thereof, which have valuable properties, particularly an inhibitory effect on cholesterol biosynthesis.
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- POLYMERIZABLE DERIVATIVES OF TRIPHENYLPHOSPHINE. ACYLATION OF TRIARYLPHOSPHINES BEARING ALCOHOL OR AMINE SUBSTITUENTS WITH ACRYLOYLCHLORIDE AND METHACRYLOYLCHLORIDE
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Methods to prepare amino substituted triaryl-phosphines viz.N-methyl-2-(diphenylphosphino)benzylamine, N-t-butyl-2-(diphenylphosphino)benzylamine and α,N-dimethyl-4-(diphenylphosphino)benzylamine are presented.The acylation of amino and alcohol substituted triarylphosphines have been studied and the amides N-methacryloyl-N-methyl-4-(diphenylphosphino)benzylamine, N-methacryloyl-2-(diphenylphosphino)aniline, N-methacryloyl-N-methyl-4-(diphenylphosphino)benzylamine, N-methyl-N-propionyl-4-(diphenylphosphino)benzylamine, N-methyl-N-propionyl-2-(diphenylphosphino)benzylamine and N-acryloyl-N-methyl-4-(diphenylphosphino)benzylamine and the ester 2-(diphenylphosphino)benzyl methacrylate have been prepared. Key words: Phosphine; monomer; acylation; acryloylchloride; methacryloylchloride polymer-bound.
- Nikitidis, Antonios,Andersson, Carlaxel
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p. 141 - 152
(2007/10/02)
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- Quantitative structure-activity relationship of the mutagenicity of substituted N-nitroso-N-benzylmethylamines: Possible implications of carcinogenicity
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The relative mutagenicities of substituted N-nitroso-N-benzylmethylamines have been reexamined from a quantitative structure-activity relationship point of view. Most of the compounds were mutagenic toward Salmonella typhimurium TA 1535 with Aroclor-induced male hamster liver S9 activation. The dose-response data were subjected to a multiple linear regression equation calculated in a stepwise manner, which found that the differences in mutagenicities could be explained primarily by differences in the three-bond path molecular connectivity index, with smaller contributions from σ and π. Moreover, a polynomial regression analysis showed that the maximum mutagenicity could be explained by an optimal amount of electron withdrawal by the substituent which could cause a weakening, or activation, of the methylene C-H bond. The possible relevance of these observations to carcinogenesis is discussed.
- Singer,Andrews,Guo
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- Oxidative N-Dealkylation of N,N-Dimethylbenzylamines by Metalloporphyrin-catalysed Model Systems for Cytochrome P450 Mono-oxygenases
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Iodosylbenzene, catalysed by tetraphenylporphyrinato-iron(III) or - manganese(III) chloride, oxidises tertiary amines by an initial one-electron transfer process whereas with t-butyl hydroperoxide with these catalysts the oxidation is initiated by hydrogen atom abstraction.
- Smith, John R. Lindsay,Mortimer, David N.
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- Benzylamines: Synthesis and evaluation of antimycobacterial properties
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The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (MIC 10.2 μg/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 μg/mL), and N-butyl-3,5-difluorobenzylamine (MIC 6.4 μg/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combination of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.
- Meindl,Von Angerer,Schonenberger,Ruckdeschel
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p. 1111 - 1118
(2007/10/02)
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